Synthesis 2018; 50(07): 1511-1520
DOI: 10.1055/s-0036-1591737
paper
© Georg Thieme Verlag Stuttgart · New York

Intramolecular Cycloaddition Approach to Fused Pyrazoles: Access to 4,5-Dihydro-2H-pyrazolo[4,3-c]quinolines, 2,8-Dihydroindeno[2,1-c]pyrazoles, and 4,5-Dihydro-2H-benzo[e]indazoles

Moumita Jash
Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata-700032, India   Email: [email protected]
,
Bimolendu Das
Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata-700032, India   Email: [email protected]
,
Suparna Sen
Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata-700032, India   Email: [email protected]
,
Chinmay Chowdhury*
Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata-700032, India   Email: [email protected]
› Author Affiliations
M.J. thanks UGC, New Delhi for a fellowship. Partial Financial support from WB-DBT (GAP 340) is gratefully acknowledged.
Further Information

Publication History

Received: 26 September 2017

Accepted after revision: 10 November 2017

Publication Date:
12 December 2017 (online)


Abstract

A straightforward and efficient method for the synthesis of pyrazoles fused with 1,2,3,4-tetrahydroquinoline, 2,3-dihydro-1H-indene­, or 1,2,3,4-tetrahydronaphthalene involves the formation of the tosylhydrazone from an aromatic substrate carrying aldehyde and acetylenic functionalities at appropriate positions, followed by base-promoted generation of the diazo compound and subsequent intramolecular 1,3-dipolar cycloaddition. A number of functional groups were found to be compatible for this reaction sequence and yields were moderate to very good (44–95%). A plausible reaction mechanism supported by DFT calculations has been provided to explain the formation of products.

Supporting Information

 
  • References

    • 1a Khan MF. Alam MM. Verma G. Akhtar W. Akhter M. Shaquiquzzaman M. Eur. J. Med. Chem. 2016; 120: 170
    • 1b Kumar H. Saini D. Jai S. Jain N. Eur. J. Med. Chem. 2013; 70: 248
    • 1c Küçükgüzel ŞG. Şenkardeş S. Eur. J. Med. Chem. 2015; 97: 786
    • 1d McDonald E. Jones K. Brough PA. Drysdale MJ. Workman P. Curr. Top. Med. Chem. 2006; 6: 1193
  • 2 Kumar V. Kaur K. Gupta GK. Sharma AK. Eur. J. Med.Chem. 2013; 69: 735

    • For example:
    • 3a Celecoxib, a COX-2 inhibitor: Hassan GS. Abou-Seri SM. Kamel G. Ali MM. Eur. J. Med. Chem. 2014; 76: 482
    • 3b Fezolamine, an antidepressant: Luttinger D. Hlasta DJ. Annu. Rep. Med. Chem. 1987; 22: 21
    • 3c Difenamizole, an analgesic: Kameyama T. Nabeshima T. Neuropharmacology 1978; 17: 249
    • 4a For anticancer activity: Wentland PM. U.S. Patent 5,334,595, 1994
    • 4b For selective cyclooxygenase-2 (COX-2) inhibitory: Baruah B. Dasu K. Vaitilingam B. Vanguri A. Casturi SR. Yeleswarapu KR. Bioorg. Med. Chem. Lett. 2004; 14: 445
    • 4c For A3 adenosine receptor antagonistic: Baraldi PG. Tabrizi MA. Preti D. Bovero Fruttarolo F. Romagnoli R. Zaid NA. Moorman AR. Varani K. Borea PA. J. Med. Chem. 2005; 48: 5001
    • 4d For phosphodiesterase-4 (PDE4) inhibitory activity: Crespo MI. Gracia J. Puig C. Vega A. Bou J. Beleta J. Domenech T. Ryder H. Segarra V. Palacios JM. Bioorg. Med. Chem. Lett. 2000; 10: 2661
    • 4e For antiulcer activity: Kalayanov GD. Kang SK. Cheon HG. Lee SG. Yum EK. Kim SS. Choi JK. Bull. Korean Chem. Soc. 1998; 19: 667
    • 4f For γ-secretase inhibitory activity: Truong AP. Aubele DL. Probst GD. Neitzel ML. Semko CM. Bowers S. Dressen D. Hom RK. Konradi AW. Sham HL. Garofalo AW. Keim PS. Wu J. Dappen MS. Wong K. Goldbach E. Quinn KP. Sauer J.-M. Brigham EF. Wallace W. Nguyen L. Hemphill SS. Bova MP. Basi G. Bioorg. Med. Chem. Lett. 2009; 19: 4920
    • 5a Skotnicki JS. Gilman CS. Steinbaugh BA. Musser JH. U.S. Patent 4,748,246, 1988 ; Chem. Abstr. 1988, 109, 110425u
    • 5b Probst G. Aubele DL. Bowers S. Dressen D. Garofalo AW. Hom RK. Konradi AW. Marugg JL. Mattson MN. Neitzel ML. Semko CM. Sham HL. Smith J. Sun M. Truong AP. Ye XM. Xu Y.-Z. Dappen MS. Jagodzinski JJ. Keim PS. Peterson B. Latimer LH. Quincy D. Wu J. Goldbach E. Ness DK. Quinn KP. Sauer J.-M. Wong K. Zhang H. Zmolek W. Brigham EF. Kholodenko D. Hu K. Kwong GT. Lee M. Liao A. Motter RN. Sacayon P. Santiago P. Willits C. Bard F. Bova MP. Hemphill SS. Nguyen L. Ruslim L. Tanaka K. Tanaka P. Wallace W. Yednock TA. Basi GS. J. Med. Chem. 2013; 56: 5261
    • 6a Murineddu G. Asproni B. Ruiu S. Deligia F. Falzoi M. Pau A. Thomas BF. Zhang Y. Pinna GA. Pani L. Lazzari P. Open Med. Chem. J. 2012; 6: 1
    • 6b Minegishi H. Fukashiro S. Ban HS. Nakamura H. ACS Med. Chem. Lett. 2013; 4: 297
    • 6c Liu Y.-N. Wang J.-J. Ji Y.-T. Zhao G.-D. Tang L.-Q. Zhang C.-M. Guo X.-L. Liu Z.-P. J. Med. Chem. 2016;  59: 5341
    • 6d Schenone S. Bruno O. Ranise A. Brullo C. Bondavalli F. Filippelli W. Mazzeo F. Capuano A. Falcone G. Farmaco 2003; 58: 845
    • 6e Meyers MJ. Arhancet GB. Hockerman SL. Chen X. Long SA. Mahoney MW. Rico JR. Garland DJ. Blinn JR. Collins JT. Yang S. Huang H.-C. McGee KF. Wendling JM. Dietz JD. Payne MA. Homer BL. Heron MI. Reitz DB. Hu X. J. Med. Chem. 2010; 53: 5979
    • 7a Jash M. Das B. Chowdhury C. J. Org. Chem. 2016; 81: 10987
    • 7b Kundu P. Mondal A. Chowdhury C. J. Org. Chem. 2016; 81: 6596
    • 7c Kundu P. Mondal A. Das B. Chowdhury C. Adv. Synth. Catal. 2015; 357: 3737
    • 7d Chowdhury C. Das B. Mukherjee S. Achari B. J. Org. Chem. 2012; 77: 5108

      For a recent review, see:
    • 8a Mekheimer RA. Ahmed EA. Sadek KU. Tetrahedron 2012; 68: 1637
    • 8b Alizadeh A. Moafi L. Ghanbaripour R. Abadi MH. Zhu Z. Kubicki M. Tetrahedron 2015; 71: 3495
    • 8c Maluleka MM. Mphahlele MJ. Tetrahedron 2013; 69: 699
    • 8d Rivilli MJ. L. Moyano EL. Yranzo GI. Tetrahedron Lett. 2010; 51: 478
    • 8e Duggineni S. Sawant D. Saha B. Kundu B. Tetrahedron 2006; 62: 3228
    • 8f Kasiotis KM. Fokialakis N. Haroutounian SA. Synthesis 2006; 1791
  • 9 Divya KV. L. Meena A. Suja TD. Synthesis 2016; 48: 4207

    • For structural isomers of dihydroindeno[2,1-c]pyrazoles 6, see:
    • 10a Zheng Y. Zhang X. Yao R. Wen YC. Huang J. Xu X. J. Org. Chem. 2016;  81: 11072
    • 10b Mor S. Nagoria S. Kumar A. Monga J. Lohan S. Med. Chem. Res. 2016; 25: 1096
    • 10c Hamilton RW. J. Heterocycl. Chem. 1976; 13: 545

      For structural isomers of 4,5-dihydrobenzo[e]indazoles 7, see:
    • 11a Péréz-Aguilar MC. Valdés C. Angew. Chem. Int. Ed. 2013; 52: 7219

    • For structurally related compounds of 7, see:
    • 11b Yang W. Ye S. Fanning D. Coon T. Schmidt Y. Krenitsky P. Stamos D. Yu J.-Q. Angew. Chem. Int. Ed. 2015; 54: 2501
    • 11c Sivaprasad G. Sridhar R. Perumal PT. J. Heterocycl. Chem. 2006; 43: 389
    • 12a Wu L.-L. Ge Y.-C. He T. Zhang L. Fu X.-L. Fu H.-Y. Chen H. Li R.-X. Synthesis 2012; 44: 1577
    • 12b Aggarwal VK. de Vicente J. Bonnert RV. J. Org. Chem. 2003; 68: 5381
    • 12c Péréz-Aguilar MC. Valdés C. Angew. Chem. Int. Ed. 2015; 54: 13729
    • 12d Kong Y. Tang M. Wang Y. Org. Lett. 2014; 16: 576
  • 13 Interestingly, it was observed that product 5f exists with its tautomeric form 5′f (see Scheme 3) in a ratio of 10:8 when NMR is recorded in DMSO-d 6; in CDCl3 this tautomerization appears to be blocked and 5f exists as a single isomer. This happens because dimethyl sulfoxide is possibly capable of making hydrogen bond with pyrazole NH leading to tautomerization.
  • 14 CCDC 1537223 (5d), CCDC 1537224 (5e), CCDC 1537225 (6b) and CCDC 1537226 (6d) contain the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 15 Savchenko TI. Silin OV. Kovalenko SM. Musatov VI. Nikitchenko VM. Ivachtchenko AV. Synth. Commun. 2007; 37: 1321